Implant-associated microbial infections are one of the most serious complications in orthopedic surgery because they are extremely difficult to treat and result in increased morbidity and substantially worse outcomes. Despite a recent focus on aseptic surgical and procedural techniques, catheter- and surgical implant-associated infections account for nearly half of the 2 million cases of nosocomial infections in the United States per year, representing a significant healthcare and economic burden. Devices and methods for imaging sub-millimeter-sized tumors that are embedded in tissues (e.g., at depths greater than 1-2 mm) are not available. Consequently, methods for treating such tumors are also lacking due to the inability in combining high specific and sensitive imaging with highly conformal radiation.’
Management of an implant-associated infection typically requires device removal, multiple debridement surgeries, and long-term systemic antibiotic therapy, despite the associated side effects and additional complications. However, these additional surgical procedures and medical therapies not only increase the healthcare costs, but also result in an increased rate of recurrence, particularly because it is difficult to clear the infection from devascularized bone and other necrotic tissues. Soon after introduction of an implant, a conditioning layer composed of host-derived adhesins (including fibrinogen, fibronectin, collagen, etc.) covers the surface of the implant. This layer promotes adherence of free-floating (planktonic) bacteria, which subsequently form an extracellular anionic polysaccharide 3 dimensional (3D) biofilm. Once a biofilm forms, it is extremely difficult to treat these infections because the biofilm blocks the penetration of both host immune cells (such as macrophages) and systemic antibiotics, promoting further bacterial survival. Given the difficulties in treating implant-associated infections, strategies aimed at preventing the infection and biofilm formation during surgery and in the immediate postoperative period may serve as more effective alternative that can prevent these infections altogether.
Prior studies have coated or covalently-linked antibiotics onto prosthetic materials to prevent bacterial infection during surgical implantation. Although this local antibiotic therapy may be effective, they are limited to certain bacterial species and these infections can be caused by a spectrum of bacteria, including Gram-positive Staphylococcus aureus, Staphylococcus epidermidis and Streptococci species, and Gram-negative Pseudomonas and Enterobacter species. Moreover, antibiotics used in this manner can contribute to the development of antibiotic resistance, which is especially relevant as there is an increasing number of infections caused by methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. epidermidis (MRSE) strains.
What is needed in the art are implant materials or coatings that can resist infection while simultaneously promoting bone growth. Such materials and/or devices made therefrom would be particularly advantageous for orthopedic surgery applications.